P675: TREATMENT OF HYPERTENSION IN PATIENTS RECEIVING BTK INHIBITORS: A MULTICENTER RETROSPECTIVE STUDY
Authors: M. Shadman, J. Voutsinas, B. Fakhri, S. Khajavian, S. Spurgeon, D. Stephens, A. Skarnbik, A. Mato, C. Broome, A. Gopal, S. Smith, R. Lynch, M. Rainey, S. Kim, O. Barrett-Campbell, E. Hemond, M. Tsang, D. Ermann, N. Malakhov, D. Rao, M. Shakib Azar, B. Morrigan, A. Chauhan, T. Plate, T. Gooley, K. Ryan, F. Lansigan, B. Hill, G. Pongas, S. Parikh, L. Roeker, J. Allan, R. Cheng, C. Ujjani
Journal: HemaSphere (2022)

Background: Hypertension (HTN) is an adverse event (AE) associated with the use of ibrutinib and less commonly with second generation BTK inhibitors (BTKis) as shown by a significant lower rate of HTN with acalabrutinib compared to ibrutinib in the ELEVATE-RR trial. Nevertheless, HTN is considered an AE of BTKis as a class. Aims: We aimed to identify a class or combination of antihypertensive drugs (anti-HTNs) that may be most effective in pts with HTN while taking a BTKi. Methods: In this multicenter retrospective real-world study, we included consecutive pts with lymphoid malignancies taking BTKis and anti-HTNs with at least 3 months of follow-up. Eligible pts were stratified into 2 groups: 1) Pts with pre-existing HTN before starting BTKi (pre-HTN) and 2) Pts who developed incident HTN after starting BTKis (de novo HTN). The anti-HTN drugs were categorized as follows: 1) Angiotensin-converting-enzyme inhibitors and Angiotensin receptor blockers (ACEi/ARB); 2) Beta-blockers (BB); 3) Calcium channel blockers (CCB); 4) Hydrochlorothiazide (HCTZ) and 5) non-HCTZ diuretics (other-DU). Timepoints for mean arterial pressure (MAP) measurements and start/end time of each anti-HTN were documented in relation to the index date (first date of concurrent use of BTKi and anti-HTN drug). Generalized estimating equations were used to assess the association between time varying MAPs and the individual drug categories, as well as the number of medication categories. Results: We included 196 pts (118 pre-HTN and 78 de novo HTN) from 12 centers. The majority of pts had CLL (94%) on ibrutinib (90%) for first (49%), second (25.5%) or later (25.5%) lines of therapy. The median age was 67 (IQR 37-88), most pts were male (72%), and caucasian (94.4%). The median duration of follow-up was 38.9 months (IQR 3.5-110). Pre-BTKi comorbidities included diabetes (17.3%), coronary disease (11.7%), cerebrovascular accidents (2.6%) and chronic kidney disease (12.8%). BTKi dose was reduced in 53 pts (27%) with 9 (4.6%) having dose reduction because of HTN. Twelve pts (6.2%) switched to other BTKis and 5 pts (2.6%) did so for HTN. In the pre-HTN cohort, a trend for statistically significant BP reduction was only achieved when 4+ anti-HTN drugs were used [Est -4.81; 95% CI (-9.93, 0.307); p = 0.07]. In this cohort, concurrent use of HCTZ and BB showed a significant trend for a lower BP [Est -5.05; 95% (-10.0, -0.06); p= 0.04]. In de novo HTN cohort, treatment with 3+ anti-HTN drugs was associated with a statistically significant reduction in the BP [Est -5.70; 95% CI (-9.94, -1.46); p =0.008]. In de novo cohort combination of HCTZ and ACEi/ARB was associated with a significant MAP reduction [Est -5.47; 95% CI (-10.9, -0.001); p= 0.05]. When the 2 cohorts were combined, treatment with 4+ drugs [Est -6.27; 95% CI (-11.8, -0.69); p = 0.02] and treatment with HCTZ and ACEi/ARB combination [Est -5.05; 95% CI (-9.61, -0.48); p = 0.03] or HCTZ and BB [Est -5.05; 95% CI(-9.61,-0.48); p= 0.03] were associated with MAP reduction. Gender or race did not modify these associations. Image:Summary/Conclusion: Treatment of HTN in pts taking Ibrutinib is challenging and requires utilization of multiple anti-hypertensive drugs both in pre-HTN and de novo HTN pts. Among different anti-HTN classes, we observed a statistically significant MAP reduction in pts with pre-HTN on HCTZ and BB combination and in pts with de novo HTN on HCTZ and ACEi/ARB combination. These findings need to be further assessed in pts taking newer generation BTKi and confirmed in large prospective studies.